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07-SEPTEMBER-2008 03:17:44 - gene It has been suggested that APC protein be merged into this article or section. Discuss Adenomatosis polyposis coli PDB rendering based on 1deb. Available structures: 1deb, 1m5i, 1th1, 1v18 Identifiers Symbols APC; DP2; DP2.5; DP3; FAP; FPC; GS External IDs OMIM: 175100 MGI: 88039 HomoloGene: 30950 Gene ontology Molecular function: beta-catenin binding microtubule binding Cellular component: nucleus cytoplasm lateral plasma membrane Biological process: protein complex assembly cell cycle cell adhesion signal transduction axis specification anterior/posterior pattern formation dorsal/ventral pattern formation Wnt receptor signaling pathway negative regulation of progression through cell cycle RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 324 11789 Ensembl ENSG00000134982 ENSMUSG00000005871 Uniprot P25054 Q8C9I9 Refseq NM_000038 mRNA NP_000029 protein XM_622559 mRNA XP_622559 protein Location Chr 5: 112.1 - 112.21 Mb Chr 18: 34.35 - 34.44 Mb Pubmed search 1 2 APC adenomatosis polyposis coli is a human gene that is classified as a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of cells that may result in cancerous tumors. The protein made by the APC gene plays a critical role in several cellular processes that determine whether a cell may develop into a tumor. The APC protein helps control how often a cell divides, how it attaches to other cells within a tissue, or whether a cell moves within or away from a tissue. This protein also helps ensure that the chromosome number in cells produced through cell division is correct. The APC protein accomplishes these tasks mainly through association with other proteins, especially those that are involved in cell attachment and signaling. The activity of one protein in particular, beta-catenin, is controlled by the APC protein see: Wnt signaling pathway. Regulation of beta-catenin prevents genes that stimulate cell division from being turned on too often and prevents cell overgrowth. The APC gene is located on the long q arm of chromosome 5 between positions 21 and 22, from base pair 112,118,468 to base pair 112,209,532. Contents 1 Related conditions 2 Regulation of Proliferation 3 Mutations 4 Neurological role 5 Further reading 6 External links Related conditions Familial adenomatous polyposis FAP is caused by mutations in the APC gene. More than 800 mutations in the APC gene have been identified in families with classic and attenuated types of familial adenomatous polyposis. Most of these mutations cause the production of an APC protein that is abnormally short and nonfunctional. This short protein cannot suppress the cellular overgrowth that leads to the formation of polyps, which can become cancerous. The most common mutation in familial adenomatous polyposis is a deletion of five bases the building blocks of DNA in the APC gene. This mutation changes the sequence of amino acids the building material of proteins in the resulting APC protein beginning at position 1309. Another mutation is carried by approximately 6 percent of people of Ashkenazi eastern and central European Jewish heritage. This mutation results in the substitution of the amino acid lysine for isoleucine at position 1307 in the APC protein also written as I1307K or Ile1307Lys. This change was initially thought to be harmless, but has recently been shown to be associated with a 10 to 20 percent increased risk of colon cancer. Regulation of Proliferation The Adenomatosis Polyposis Coli APC protein normally builds a complex with glycogensynthasekinase 3betaGSK 3β and Axin via interactions with the 20AA and SAMP repeats. This complex is then able to bind β- catenins in the cytoplasm, that have dissociated from adherens contacts between cells. With the help of Casein Kinase 1 CK1 which does the first phosphorylation of β-catenin, there is subsequent phosphorylation by GSK-3β. This targets β-catenin for ubuiquitination and degradation by cellular proteosomes. This prevents it from translocating into the nucleus, where it acts as a transcription factor for proliferation genes. APC is also thought to be targeted to microtubules via the PDZ binding domain, stabilising them. The deactivation of the APC protein can take place after certain chain reactions in the cytoplasm are started, e.g. through the Wnt signals that destroy the conformation of the complex. In the nucleus it complexes with legless/BCL9, TCF, and Pygo and begins function of an RNA polymerase but for oncogenes. Mutations Mutations in APC often occur early on in cancers such as colon cancer. Patients with familial adenomatous polyposis FAP have germline mutations, with 95% being nonsense/frameshift mutations leading to premature stop codons. 33% of mutations occur between amino acids 1061-1309. In somatic mutations, over 60% occur within a mutation cluster region 1286-1513, causing loss of axin binding sites in all but 1 of the 20AA repeats. Mutations in APC lead to loss of β-catenin regulation, altered cell migration and chromosome instability. Neurological role Rosenberg et al. found that APC directs cholinergic synapse assembly between neurons, a finding with implications for autonomic neuropathies, for Alzheimer's disease, for age-related hearing loss, and for some forms of epilepsy and schizophrenia. Further reading Cohen MM Jr 2003. Molecular dimensions of gastrointestinal tumors: some thoughts for digestion. Am J Med Genet A 122 4: 303-14. doi:10.1002/ajmg.a.20473. PMID 14518068. Fearnhead NS, Britton MP, Bodmer WF 2001. The ABC of APC. Hum Mol Genet 10 7: 721-33. doi:10.1093/hmg/10.7.721. PMID 11257105. Fodde R 2002. The APC gene in colorectal cancer. Eur J Cancer 38 7: 867-71. doi:10.1016/S0959-80490200040-0. PMID 11978510. Goss KH, Groden J 2000. Biology of the adenomatous polyposis coli tumor suppressor. J Clin Oncol 18 9: 1967-79. PMID 10784639. Jarvinen HJ, Peltomaki P 2004. The complex genotype-phenotype relationship in familial adenomatous polyposis. Eur J Gastroenterol Hepatol 16 1: 5-8. doi:10.1097/00042737-200401000-00002. PMID 15095846. Lal G, Gallinger S 2000. Familial adenomatous polyposis. Semin Surg Oncol 18 4: 314-23. doi:10.1002/SICI1098-238820000618:4314::AID-SSU63.0.CO;2-9. PMID 10805953. van Es JH, Giles RH, Clevers HC 2001. The many faces of the tumor suppressor gene APC. Exp Cell Res 264 1: 126-34. doi:10.1006/excr.2000.5142. PMID 11237529. Rosenberg MM, Yang F, Giovanni M, Mohn J, Temburni MK, Jacob M 2008-06. Adenomatous polyposis coli plays a key role, in vivo, in coordinating assembly of the neuronal nicotinic postsynaptic complex.. Molecular and Cellular Neuroscience 38 2: 138-152. doi:10.1016/j.mcn.2008.02.006. External links MeSH Adenomatous+Polyposis+Coli+Protein GeneCard v d e Tumor suppressor genes/proteins Cell membrane/cytosol Neurofibromin 1 - Neurofibromin 2/Merlin - APC - PTEN Mitochondria SDHB - SDHD Nucleus pRb - p16 - p53 - BRCA1 - BRCA2 - Cell cycle CHEK2, p14arf, p21, p27, p57, p73 Other/ungrouped Maspin - VHL v d e Proteins of the cytoskeleton Microfilaments Actins - Actin-binding proteins - Actinin - Arp2/3 complex - Cofilin - Destrin - Gelsolin - Myosins - Profilin - Tropomodulin - Troponin T, C, I - Tropomyosin - Wiskott-Aldrich syndrome protein Intermediate filaments type 1 and 2 Cytokeratin, type I, type II - type 3 Desmin, GFAP, Peripherin, Vimentin - type 4 Internexin, Nestin, Neurofilament, Synemin, Syncoilin - type 5 Lamin A, B Microtubules Dyneins - Kinesins - MAPs Tau protein, Dynamin - Tubulins - Stathmin - Tektin Catenins Alpha catenin - Beta catenin - Plakoglobin gamma catenin - Delta catenin Nonhuman Major sperm proteins - Prokaryotic cytoskeleton Crescentin, FtsZ, MreB Other APC - Dystrophin Dystroglycan - plakin Desmoplakin, Plectin - Spectrin - Talin - Utrophin - Vinculin Retrieved from http://en..org/wiki/APC_gene Categories: Genes on chromosome 5 | Human proteins | Genes | Tumor suppressor genesHidden category: Articles to be merged since November 2007 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Polski This page was last modified on 8 July 2008, at 01:54
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